Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts
Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts
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DOI：
10.1016/j.ydbio.2015.05.012
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发表时间：
2015-08-15
影响因子：
2.7
通讯作者：
Lemaigre, Frederic P.
中科院分区：
文献类型：
--
作者：
Poncy, Alexis;Antoniou, Aline;Lemaigre, Frederic P.
在发育中的肝脏中，胆管细胞来源于肝母细胞并组织形成胆管。早期的研究表明，SRY相关的高迁移率族盒转录因子9（SOX 9）是短暂需要胆管发育，提出了其他SOX家族成员在胆管形态发生的潜在参与的问题。在这里，我们确定SOX 4作为胆管细胞发育的新调节因子。肝脏特异性SOX 4失活，结合或不结合SOX 9失活，影响胆管细胞分化，顶端-基底极性和胆管形成。这两种因子共同控制转化生长因子-β、Notch和Hippo-Yap信号通路的介质的表达，这些介质是胆管正常发育所需的。此外，SOX 4和SOX 9控制初级纤毛的形成，它们是已知的信号调节剂。这两种因子还刺激层粘连蛋白α 5的分泌，层粘连蛋白α 5是促进胆管成熟的细胞外基质成分。我们的结论是，SOX 4是一个新的调节肝脏发育，它发挥了多效性控制胆管发育与SOX 9合作。(C)2015 Elsevier Inc. All rights reserved.
In developing liver, cholangiocytes derive from the hepatoblasts and organize to form the bile ducts. Earlier work has shown that the SRY-related High Mobility Group box transcription factor 9 (SOX9) is transiently required for bile duct development, raising the question of the potential involvement of other SOX family members in biliary morphogenesis. Here we identify SOX4 as a new regulator of cholangiocyte development. Liver-specific inactivation of SOX4, combined or not with inactivation of SOX9, affects cholangiocyte differentiation, apico-basal polarity and bile duct formation. Both factors cooperate to control the expression of mediators of the Transforming Growth Factor-beta, Notch, and Hippo-Yap signaling pathways, which are required for normal development of the bile ducts. In addition, SOX4 and SOX9 control formation of primary cilia, which are known signaling regulators. The two factors also stimulate secretion of laminin alpha 5, an extracellular matrix component promoting bile duct maturation. We conclude that SOX4 is a new regulator of liver development and that it exerts a pleiotropic control on bile duct development in cooperation with SOX9. (C) 2015 Elsevier Inc. All rights reserved.